Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized ce...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/105238 http://hdl.handle.net/10220/47896 |
| _version_ | 1826129156609409024 |
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| author | Segal, Joe M. No, Da Yoon Saeb-Parsy, Kourosh Serra, Maria Paola Horcas-Lopez, Marta Mastoridis, Sotiris Jassem, Wayel Frank, Curtis W. Nakauchi, Hiromitsu Glenn, Jeffrey S. S. Tamir Rashid Ng, Soon Seng Blackford, Samuel J. I. Cho, Nam Joon |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Segal, Joe M. No, Da Yoon Saeb-Parsy, Kourosh Serra, Maria Paola Horcas-Lopez, Marta Mastoridis, Sotiris Jassem, Wayel Frank, Curtis W. Nakauchi, Hiromitsu Glenn, Jeffrey S. S. Tamir Rashid Ng, Soon Seng Blackford, Samuel J. I. Cho, Nam Joon |
| author_sort | Segal, Joe M. |
| collection | NTU |
| description | Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications. |
| first_indexed | 2024-10-01T07:36:06Z |
| format | Journal Article |
| id | ntu-10356/105238 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:36:06Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1052382023-07-14T15:56:16Z Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold Segal, Joe M. No, Da Yoon Saeb-Parsy, Kourosh Serra, Maria Paola Horcas-Lopez, Marta Mastoridis, Sotiris Jassem, Wayel Frank, Curtis W. Nakauchi, Hiromitsu Glenn, Jeffrey S. S. Tamir Rashid Ng, Soon Seng Blackford, Samuel J. I. Cho, Nam Joon School of Materials Science & Engineering DRNTU::Science::Biological sciences Biomimetic Materials Liver Stem Cells Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications. NRF (Natl Research Foundation, S’pore) Published version 2019-03-25T07:12:43Z 2019-12-06T21:47:50Z 2019-03-25T07:12:43Z 2019-12-06T21:47:50Z 2018 Journal Article Ng, S. S., Saeb-Parsy, K., Blackford, S. J. I., Segal, J. M., Serra, M. P., Horcas-Lopez, M., . . . S. Tamir Rashid. (2018). Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold. Biomaterials, 182, 299-311. doi:10.1016/j.biomaterials.2018.07.043 0142-9612 https://hdl.handle.net/10356/105238 http://hdl.handle.net/10220/47896 10.1016/j.biomaterials.2018.07.043 en Biomaterials © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 13 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Biomimetic Materials Liver Stem Cells Segal, Joe M. No, Da Yoon Saeb-Parsy, Kourosh Serra, Maria Paola Horcas-Lopez, Marta Mastoridis, Sotiris Jassem, Wayel Frank, Curtis W. Nakauchi, Hiromitsu Glenn, Jeffrey S. S. Tamir Rashid Ng, Soon Seng Blackford, Samuel J. I. Cho, Nam Joon Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title_full | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title_fullStr | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title_full_unstemmed | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title_short | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
| title_sort | human ips derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly ethylene glycol scaffold |
| topic | DRNTU::Science::Biological sciences Biomimetic Materials Liver Stem Cells |
| url | https://hdl.handle.net/10356/105238 http://hdl.handle.net/10220/47896 |
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